There is convincing evidence that exercise protects against breast cancer but the mechanisms involved are largely unknown. The overall objective of this application is to determine how regular exercise affects melatonin secretion. The long-term goal is to understand how exercise affects factors associated with breast cancer risk. The central hypothesis is that regular exercise increases melatonin levels in young women, and this effect may be modulated by exposure to light at night, stress, and sleep. Our rationale for this project is that once we learn the relationship between exercise and melatonin production, and how light, stress, and sleep may influence this relationship, we will be able to explore this relationship in different populations and gain a better understanding of the mechanisms by which exercise may protect against breast cancer in women. To test the central hypothesis and accomplish the overall objective of this application the following specific aims will be pursued: 1) Determine the effect of regular exercise on melatonin secretion and excretion in young women by testing the hypothesis that regular aerobic exercise for 4 menstrual cycles will produce persisting higher levels of both plasma melatonin and urinary 6-sulfatoxymelatonin (primary metabolite of melatonin) compared to young women who have not engaged in regular exercise;and 2) Evaluate and characterize factors associated with melatonin secretion and excretion. In order to accomplish these aims, plasma melatonin will be measured by radioimmunoassay and urinary 6-sulfatoxymelatonin, cortisol, epinephrine and norepinephrine will be measured by enzyme-linked immunosorbent assay. All measurements will be done before and following the exercise intervention. Participants will also be asked to fill out sleep journals and a sleep quality survey, before and following the exercise intervention. The sleep journals will provide information about time and duration of sleep as well as light exposure at night. This project is innovative because the effects of regular exercise on melatonin secretion have not yet been studied in a controlled clinical trial. Furthermore, we are proposing to measure several variables that are clearly associated with melatonin secretion but have been overlooked by previous studies, such as sleep duration. The proposed research is significant because it will provide the knowledge needed to develop effective interventions to maximize the benefits of exercise for breast cancer prevention. PUBLIC HEALTH RELEVANCE: The proposed study will contribute to better understanding of the relationship between energy balance, sleep and breast cancer prevention in women, which will have a positive impact on women's quality of life and health. This research is also expected to be applicable to prevention of other types of cancers, as well as a broader spectrum of chronic diseases.